ATP4A: The Gastric Proton Pump Alpha Subunit
A key gene in gastric acid secretion, linked to autoimmune gastritis and gastric cancer risk.
Gene Information Card
| Symbol | ATP4A |
|---|---|
| Full Name | ATPase H+/K+ transporting subunit alpha |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.33 |
| NCBI Gene ID | 495 ncbi.nlm.nih.gov/gene/495 |
| Ensembl ID | ENSG00000105675 |
| UniProt ID | P20648 |
| OMIM ID | 137216 |
| HGNC ID | 819 |
| Aliases | ATP6A, ATP6B, H+/K+ ATPase alpha subunit |
Description
ATP4A encodes the alpha subunit of the gastric H+/K+ ATPase, a proton pump responsible for gastric acid secretion. This enzyme is a heterodimer composed of a catalytic alpha subunit (ATP4A) and a glycosylated beta subunit (ATP4B). It is primarily expressed in gastric parietal cells and is essential for acidifying the stomach lumen. Mutations and autoimmune targeting of ATP4A are associated with achlorhydria, autoimmune gastritis, and increased risk of gastric neoplasia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autoimmune gastritis | Autoantibodies against ATP4A lead to parietal cell destruction and achlorhydria. | ClinVar, OMIM |
| Gastric cancer | Loss of ATP4A function causes chronic hypochlorhydria, hypergastrinemia, and enterochromaffin-like cell hyperplasia, predisposing to neuroendocrine tumors and adenocarcinoma. | NCBI Gene, OMIM |
| Pernicious anemia | Autoimmune destruction of parietal cells reduces intrinsic factor, leading to vitamin B12 deficiency. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Stomach | 78.5 | High |
| Esophagus | 0.8 | Low |
| Duodenum | 0.5 | Low |
| Pancreas | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| AGS (gastric adenocarcinoma) | 12.3 | Moderate expression |
| MKN45 (gastric cancer) | 8.7 | Moderate expression |
| HEK293 (embryonic kidney) | 0.0 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.244G>A (p.Gly82Arg) | Missense | Rare | Reported in gastric cancer; may impair pump function |
| c.376C>T (p.Arg126Trp) | Missense | Rare | Associated with autoimmune gastritis |
| c.1939G>A (p.Glu647Lys) | Missense | Rare | Functional impact unknown |
Mutation functional classification
Loss of Function (LOF)
Missense mutations in ATP4A can disrupt proton transport, leading to achlorhydria and hypergastrinemia.
Gain of Function (GOF)
Not described in literature.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
| • P-type proton-exporting transporter activity (GO:0005391) | • proton transmembrane transport (GO:0015992) |
| • plasma membrane (GO:0005886) | • gastric acid secretion (GO:0001696) |
| • proton-transporting ATP synthase activity (GO:0046933) |
Pathways
• REACTOME: Gastric acid secretion (R-HSA-427589)
• KEGG: Gastric acid secretion (hsa04971)
• KEGG: Collecting duct acid secretion (hsa04966)
Protein Summary
The ATP4A protein (UniProt P20648) is a 1035-amino acid multi-pass membrane protein that forms the catalytic core of the gastric H+/K+ ATPase. It contains 10 transmembrane domains and uses ATP hydrolysis to exchange cytoplasmic H+ for luminal K+, generating a proton gradient of up to 10^6-fold. This pump is the pharmacological target of proton pump inhibitors (e.g., omeprazole).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATP4A Knockout HEK293 Cell Line | EDJ-KQ12132 | Human | 495 | Details Get a Quote |
| ATP4A Knockout HeLa Cell Line | EDJ-KQ52687 | Human | 495 | Details Get a Quote |
| ATP4A Knockout A-549 Cell Line | EDJ-KQ61158 | Human | 495 | Details Get a Quote |
| ATP4A Knockout HCT 116 Cell Line | EDJ-KQ69646 | Human | 495 | Details Get a Quote |
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